The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate
Open accessAbstract
The gut microbiota produces metabolites such as short-chain fatty acids (SCFAs) that regulate the energy homeostasis and impact on immune cell function of the host. Recently, innovative approaches based on the oral administration of SCFAs have been discussed for therapeutic modification of inflammatory immune responses in autoimmune diseases. So far, most studies have investigated the SCFA-mediated effects on CD4+ T cells and antigen presenting cells. Here we show that butyrate and, to a lesser degree, propionate directly modulate the gene expression of CD8+ cytotoxic T lymphocytes (CTLs) and Tc17 cells. Increased IFN-γ and granzyme B expression by CTLs as well as the molecular switch of Tc17 cells towards the CTL phenotype was mediated by butyrate independently of its interaction with specific SCFA-receptors GPR41 and GPR43. Our results indicate that butyrate strongly inhibited histone-deacetylases (HDACs) in CD8+ T cells thereby affecting the gene expression of effector molecules. Accordingly, the pan-HDAC inhibitors trichostatin A (TSA) and sodium valproate exerted similar influence on CD8+ T cells. Furthermore, higher acetate concentrations were also able to increase IFN-γ production in CD8+ T lymphocytes by modulating cellular metabolism and mTOR activity. These findings might have significant implications in adoptive immunotherapy of cancers and in anti-viral immunity.
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Cites
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
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The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
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Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
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Gut Microbial Metabolites Fuel Host Antibody Responses
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Kimura, I., Ichimura, A., Ohue-Kitano, R., & Igarashi, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,018
He, Y., Fu, L., Li, Y., Wang, W., Gong, M., Zhang, J., Dong, X., Huang, J., Wang, Q., Mackay, C. R., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.002 · Cited by 729
Gut microbiota in colorectal cancer development and therapy
Wong, C. C., & Yu, J. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00766-x · Cited by 721
Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
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Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids
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Metadata
- Authors
- Luu, M., Weigand, K., Wedi, F., Breidenbend, C., Leister, H., Pautz, S., Adhikary, T., & Visekruna, A.
- Venue
- Scientific Reports
- Published
- 2018-09-26
- Volume
- 8
- Issue
- 1
- Pages
- 14430-14430
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2890880452
- Cited by
- 342
- References
- 11
- FWCI
- 8.55
- Type
- journal article
- Language
- en
- Open access
- gold
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- Luu, M., Weigand, K., Wedi, F., Breidenbend, C., Leister, H., Pautz, S., Adhikary, T., & Visekruna, A. (2018). Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate. Scientific Reports. https://doi.org/10.1038/s41598-018-32860-x
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